Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease

NCT ID: NCT01014858

Last Updated: 2017-09-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2014-09-30

Brief Summary

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To demonstrate the superiority of donepezil over placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment.

To demonstrate the superiority of donepezil over placebo in improving patient and carer quality of life and to establish the cost-effectiveness of donepezil.

To determine the instrument most suitable for evaluating change in cognition in people with Parkinson's disease and mild dementia.

Detailed Description

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Conditions

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Parkinson's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Donepezil

5mg of Donepezil for the first 8 weeks raising to 10mg thereafter if patient adjusted to 5mg dose. 10mg does continues for the remainder of the study.

Group Type EXPERIMENTAL

Donepezil

Intervention Type DRUG

5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study.

Placebo

Patient commences medication to match appearance of 5mg donepezil for first 8 weeks then 10mg for the remainder of the study.

Group Type PLACEBO_COMPARATOR

Donepezil

Intervention Type DRUG

5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study.

Interventions

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Donepezil

5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. A diagnosis of Parkinson's disease according to UK Parkinson's Disease Society Brain Bank Criteria. These criteria are in standard use throughout the NHS in the UK and were supported by the NICE guidelines.
2. People with mild dementia associated with PD, where the patient and/or their family have become aware of cognitive with or without behavioural symptoms that are causing functional impairment. "Dementia" will be defined according to recently published Movement Disorder Society Task Force criteria for dementia associated with Parkinson's Disease and "operationalised" using the Addenbrooke's Cognitive Examination (ACE-R). The ACE-R permits some description of the dementia profile and also quantifies global impairment. It is increasingly used by clinicians in the UK to identify demented subjects, is relatively quick to perform (15 minutes or so), requires no specific training and produces a total score (0-100), from which the MMSE (0-30) can also be extracted. Participants will have an ACE-R of 88 or less. If this criterion is met, subjects will be further assessed using the Mattis Dementia Rating Scale (DRS-2). An age- and education-corrected total DRS-2 score of less than 8 but greater than 4 (corresponding to between the 6th and 28th percentile) will be used to define "mild" dementia".
3. Community-living and a spouse, close relative or well established carer to accompany the subject to act as an informant.
4. Where relevant, women of child bearing potential must be using adequate contraception for duration of study.

Exclusion Criteria

1. Dementia that develops within one year of the onset of motor symptoms. The reason for this "one year rule" is to specifically exclude participants with Dementia with Lewy Bodies (DLB). This exclusion criterion is consistent with recommendations made in the Movement Disorder Society Dementia Task Force Diagnostic Criteria and the Third Report of the DLB Consortium.
2. People with such severe motor disability, or who are so impaired in their activities of daily living from other aspects of their PD, that it would interfere with cognitive and global assessments.
3. Severe current depressive episode. Low mood may impact upon accurate cognitive assessment and major depression is therefore listed as a feature which, when present, makes it impossible to reliably diagnose PDD in the Movement disorder Society Task Force PDD Criteria. This will be operationalised using the self-completed Beck Depression Inventory and a cut-off score of 13, as recommended by a recent Movement Disorder Society Task Force report. The BDI score is considered robust in the face of mild to moderate cognitive impairment.
4. Unstable significant medical co-morbidity.
5. Patient receiving an anticholinergic drug for control of parkinsonian motor symptoms.
6. Previous exposure to a cholinesterase inhibitor
7. Presence of a condition that is contraindicative to use of donepezil (including a clinically significant cardiac conduction defect found in patient history or from screening ECG); see SmPC (Appendix W) for details.
8. Allergy/hypersensitivity to excipients of donepezil or placebo
9. Patient receiving the N-methyl-d-aspartate antagonist memantine.
10. Previous neurosurgery for Parkinson's disease. This will apply to only a small minority of predominantly younger cases. The main reason for this exclusion relates to ongoing uncertainty over the potential confounding effects of deep brain stimulation upon both mood and cognition.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Newcastle Upon-Tyne

OTHER

Sponsor Role collaborator

University of Cambridge

OTHER

Sponsor Role collaborator

University of Manchester

OTHER

Sponsor Role collaborator

University of Birmingham

OTHER

Sponsor Role collaborator

Bangor University

OTHER

Sponsor Role collaborator

London School of Economics and Political Science

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Lancashire Care NHS Foundation Trust

NETWORK

Sponsor Role collaborator

Newcastle University

OTHER

Sponsor Role collaborator

King's College London

OTHER

Sponsor Role collaborator

Newcastle-upon-Tyne Hospitals NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David J Burn, Professor

Role: STUDY_CHAIR

Newcastle University

Roger A Barker, Dr

Role: STUDY_DIRECTOR

Cambridge University

Belinda Braithwaite, Mrs

Role: STUDY_DIRECTOR

lay person

Alistair Burns, Professor

Role: STUDY_DIRECTOR

School of Community Based Medicine, University of Manchester

Carl E Clarke, Professor

Role: STUDY_DIRECTOR

Clarke

Elaine McColl, Professor

Role: STUDY_DIRECTOR

University of Newcastle Upon-Tyne

John V Hindle, Dr

Role: STUDY_DIRECTOR

Llandudno Hospital & University of College Wales

Martin Knapp, Professor

Role: STUDY_DIRECTOR

London School of Economics and Political Science

Andrew J Lees, Professor

Role: STUDY_DIRECTOR

University College, London

Iracema Leroi, DR

Role: STUDY_DIRECTOR

Lancashire Care Trust, Royal Blackburn Hospital

Ian G McKeith, Professor

Role: STUDY_DIRECTOR

Newcastle University

John T O'Brien, Professor

Role: STUDY_DIRECTOR

Newcastle University

Keith Wheatley, Professor

Role: STUDY_DIRECTOR

Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham

Ian N Steen, Dr

Role: STUDY_DIRECTOR

University of Newcastle Upon-Tyne

Jennifer Wilkinson, Mrs

Role: STUDY_DIRECTOR

University of Newcastle Upon-Tyne

Sharon Erb, Mrs

Role: STUDY_DIRECTOR

University of Newcastle Upon-Tyne

Daniel Weintraub

Role: STUDY_DIRECTOR

Associate Professor of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania

Lynn Rochester

Role: STUDY_DIRECTOR

Professor of Human Movement Science, Institute for Ageing and Health, Newcastle University

Locations

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Newcastle

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Site Status

Royal United Hospital (RUH) Bath NHS

Bath, , United Kingdom

Site Status

Sandwell and West Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Steps and Pines, Southmead Hospital

Bristol, , United Kingdom

Site Status

Pennine Acute Hospitals NHS Trust

Bury, , United Kingdom

Site Status

Cambridge Centre for Brain Repair

Cambridge, , United Kingdom

Site Status

Dr Lakmali Sugathapala

Derby, , United Kingdom

Site Status

Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust

Dorset, , United Kingdom

Site Status

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status

Dr Pippa Metcalf

Gloucester, , United Kingdom

Site Status

Llandudno Hospital, Betsi Cadwaladr University Health Board & School of Medical Sciences

Llandudno, , United Kingdom

Site Status

King's College Hospital NHS Foundtion Trust

London, , United Kingdom

Site Status

Manchester Mental Health & Social Care NHS Trust

Manchester, , United Kingdom

Site Status

Milton Keynes

Milton Keynes, , United Kingdom

Site Status

Royal Gwent Hospital

Newport, , United Kingdom

Site Status

North Tyneside General Hospital

Northumberland, , United Kingdom

Site Status

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, , United Kingdom

Site Status

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Site Status

Plymouth Hospitals NHS Trust

Plymouth, , United Kingdom

Site Status

Poole Hospital NHS Trust

Poole, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Dr Dhakam

Surrey, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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08/13/14

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

5137

Identifier Type: -

Identifier Source: org_study_id